Noradrenaline Acid Tartrate (link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/noradrenaline-acid-tartrate-cas-69815-49-2.html) is a common compound with a wide range of applications in medicine. In addition to the methods mentioned above, there are several other common synthetic methods for a brief introduction.
1. Sulphite reaction method:
This method reacts norepinephrine with thionyl chloride under alkaline conditions to generate norepinephrine sulfinyl salt and hydrochloric acid. Then, norepinephrine sulfinyl salt is reacted with tartaric acid to obtain Noradrenaline Acid Tartrate.
Reaction steps:
Step 1: Thionyl Chlorination Reaction
Reaction of norepinephrine with thionyl chloride under alkaline conditions produces norepinephrine sulfinyl salt and hydrochloric acid. The reaction is usually performed in an inert solvent such as dimethylsulfoxide (DMSO) or dimethylformamide (DMF). Reaction conditions may include appropriate temperature and reaction time.
Chemical formula:
C8H11NO3.C4H6O6 + SOCl2 + 2 NaOH → Noradrenaline Sulfinyl Chloride + 2 NaCl + H2O
Step 2: Tartrate reaction
Noradrenaline Acid Tartrate is produced by reacting norepinephrine sulfinyl salt with tartaric acid. This step is usually performed in a solvent and may require appropriate temperatures and reaction times.
Chemical formula:
Noradrenaline Sulfinyl Chloride + C4H6O6 → C8H11NO3.C4H6O6
Step 3: Crystallization and Purification
After Noradrenaline Acid Tartrate is obtained, a product with higher purity can be obtained through crystallization and purification steps. This usually involves the choice of solvent, optimization of crystallization conditions, and steps of filtration and drying of crystals.
2. Decarboxylation reaction method:
The method takes decarboxylation reaction as the key step. First, norepinephrine is reacted with acetone acetic anhydride (acetic anhydride) and pyridine (pyridine) to generate substituted ethyl carboxylate. The ethyl substituted carboxylate is then decarboxylated by acid catalysis or pyrolysis to yield norepinephrine. Finally, Noradrenaline Acid Tartrate is synthesized by reacting norepinephrine with tartaric acid.
Reaction steps:
Step 1: Esterification reaction
Norepinephrine is reacted with acetone acetic anhydride and pyridine to form ethyl substituted carboxylate of norepinephrine. The reaction is usually performed in an inert solvent such as dichloromethane or dimethylformamide (DMF). Reaction conditions include appropriate temperature and reaction time.
Chemical formula:
C8H11NO3.C4H6O6 + Acetic Anhydride + Pyridine → Noradrenaline Acetate Ester + C5H5N.ClH
Step 2: Decarboxylation reaction
Norepinephrine is produced by decarboxylation of ethyl substituted carboxylates of norepinephrine by acid catalysis or pyrolysis. The decarboxylation reaction is usually carried out under acidic conditions, such as using concentrated sulfuric acid or trifluoroacetic acid. Reaction conditions may also involve appropriate temperature and reaction time.
Chemical formula:
Noradrenaline Acetate Ester + H2O → C8H11NO3.C4H6O6 + C2H4O2
Step 3: Reaction with tartaric acid
Noradrenaline Acid Tartrate is produced by reacting the obtained norepinephrine with tartaric acid. The reaction is usually carried out in a solvent and may require appropriate temperature and reaction time.
Chemical formula:
C8H11NO3.C4H6O6 + C2H4O2 → C12H19NO10
Step 3. Crystallization and purification
Through the steps of crystallization and purification, the Noradrenaline Acid Tartrate product with higher purity can be obtained. This usually involves the choice of solvent, optimization of crystallization conditions, and steps of filtration and drying of crystals.
3. Pasteur-Müller reaction method:
This method takes the Pasteur-Miller reaction as the key step, and reacts heteroaminomethane (formamidine) with p-nitroacetophenone (p-nitroacetophenone) to generate Pasteur ammonia (Bart's amine). Then, Pasteur ammonia reacts with tartaric acid to obtain Noradrenaline Acid Tartrate through reduction and crystallization.
Reaction steps:
Step 1: Esterification reaction
Mix norepinephrine with diethyl tartrate and carry out esterification reaction in an appropriate solvent. This step requires an inert atmosphere to prevent oxidation.
Chemical formula:
C8H11NO3.C4H6O6 + C8H14O6 → Noradrenaline Diethyl Tartrate
Step 2: Hydrolysis reaction
React the obtained Noradrenaline Diethyl Tartrate with sodium hydroxide (or other alkali) solution for hydrolysis. This reaction produces Noradrenaline Acid Tartrate and ethanol.
Chemical formula:
Noradrenaline Diethyl Tartrate + NaOH + H2O → C8H11NO3.C4H6O6 + C2H6O + C4H4Na2O6 Step 3: Thiolysis reaction
Dissolve Noradrenaline Acid Tartrate in ethanol, then add a certain amount of sulfur fumigant (or other suitable reducing agent) to the solution for thiolysis reaction. This reaction reduces Noradrenaline Acid Tartrate to Noradrenaline.
Chemical formula:
C8H11NO3.C4H6O6 + S8 + C2H6O → C8H11NO3.C4H6O6 + CO2 + O2S + H2O
3. Crystallization and Purification
Through the steps of crystallization and purification, the Noradrenaline Acid Tartrate product with higher purity can be obtained. This usually involves the choice of solvent, optimization of crystallization conditions, and steps of filtration and drying of crystals.
4. Hydroxylamine synthesis method:
The method uses amphetamine (phenylpropanolamine) as a precursor, which is converted into norepinephrine through a series of reactions, and then reacts with tartaric acid to form Noradrenaline Acid Tartrate. This method is relatively complex and requires multiple steps to complete.
Reaction steps:
Step 1: Synthesis of hydroxylamine precursor
The 3,4-dihydroxyacetophenone reacts with sodium hydroxide to generate the corresponding alkoxide. The reaction is usually performed under an inert atmosphere to prevent oxidation.
Chemical formula:
C9H10O3 + NaOH → Dihydroxyphenylacetone Sodium Salt
Step 2: Reduction reaction
The obtained alkoxide is reacted with sodium bisulfite, and the reduction reaction is carried out under alkaline conditions to generate hydroxylamine derivatives. Sodium bisulfite acts as a reducing agent in this reaction.
Chemical formula:
Dihydroxyphenylacetone Sodium Salt + HNaO3S → Hydroxylamine Derivative + Na2O3S
Step 3: Reaction with tartaric acid
The resulting hydroxylamine derivative is reacted with tartaric acid to produce Noradrenaline Acid Tartrate. The reaction is usually carried out in a solvent and may require appropriate temperature and reaction time.
Chemical formula:
Hydroxylamine Derivative + C4H6O6 → C8H11NO3.C4H6O6
Step Four: Acidification and Neutralization
Dissolve Noradrenaline Acid Tartrate in absolute ethanol, then add hydrochloric acid dropwise to acidify the solution. The solution is then neutralized with an appropriate amount of alkaline solution until the pH reaches the desired range.
3. Crystallization and Purification
Through the steps of crystallization and purification, the Noradrenaline Acid Tartrate product with higher purity can be obtained. This usually involves the choice of solvent, optimization of crystallization conditions, and steps of filtration and drying of crystals.